THz and mm-Wave Sensing of Corneal Tissue Water Content: In Vivo Sensing and Imaging Results

Abstract

A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10× higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo.

Keywords: Biological and medical imaging; clinical instruments; medical diagnostics; tissue water content interactions.

Fig. 1

Millimeter wave reflectometer. (a) System block diagram. (b) Illumination geometry (c) biasing scheme demonstrating low frequency chopping combined with high frequency FMCW.

Fig. 2

THz imaging system. (a) System block diagram. (b) Illumination geometry. (c) Photoconductive switch power spectral density and detector spectral responsivity.

Fig. 3

Sensitivity analysis of the millimeter wave sensing system (left) and THz imaging system (right). Millimeter wave data from [14] and THz data from [3].

Fig. 4

Imaging results of corneal geometry phantom (PTFE sphere). (left) THz image of the sphere with the imaging axis parallel to the normal of the sphere apex. (right) Horizontal and vertical cuts through the image superimposed with Gaussian fits.

Fig. 5

Rabbit cornea imaging. (top) Rabbit model placed below the THz and millimeter-wave imaging systems. (bottom) Close-up of rabbit cornea and mylar window.

Fig. 6

Comparison of CCT to CTWC percentage relation for rabbit cornea [see (3)] and human cornea [see (4)].

Fig. 7

CCT measurements for all rabbits in the trial and their associated CTWC levels computed with (3). Rabbit 5 has a large outlier at time 50 min which was not included in the linear fits.

Fig. 8

100 GHz point measurements plotted against the CCT measurements reflected in the lower x-axis. The corresponding CTWC increases predicted by CCT theory are displayed on the top x-axis.

Fig. 9

Selected THz reflectivity maps of CTWC for all five rabbit models. Each image series is accompanied by its CCT range and computed CTWC levels using (3) Time increases, from left to right and top to bottom for each image series. The dotted circles overlaid on the top left cornea of each image denote the ultrasound probe location.

Fig. 10

THz reflectivities computed with the indicated region of interest as a function of acquired CCT measurements reflected in the lower x-axis. The corresponding CTWC increases predicted by CCT theory are displayed on the top x-axis. A zoom-in of the first point in the rabbit 4 series is displayed in the inset demonstrating the difference in variation between estimated system noise and contrast observed in the 5 mm diameter FOV.

Fig. 11

Dependence of corneal reflectivity on TWC and thickness computed for the (left column) 100 GHz system and (right column) 525 GHz system for the gradient types (top row) pinned front, (middle row) pinned back, and (bottom row) global. The figures within each row are displayed with a common colormap, with pixel intensities representing reflectivity.

Fig. 12

Constant CTWC cuts at 79% water by weight with varying distance over the range measured by ultrasound pachymetry. Note that in the case of constant CTWC-varying CCT the three gradient types yield the same behavior which is represented by the solid line.

Fig. 13

Post mortem study. (left) Observed change in reflectivity at 100 GHz per change in CCT. (right) Predicted change in reflectivity for the pinned front gradient case.